|
|
|
Statement from W. John Martin, M.D., Ph.D.
I have generally disregarded the mean spirited and erroneous criticisms that have been leveled against me and against the existence of stealth-adapted viruses. The individuals making or regurgitating the criticisms should never have been taken seriously. Unfortunately, negative comments are accessible on the internet and undoubtedly have caused considerable confusion and concern. In the interests of people reading such comments, I have decided to briefly discuss i) evidence for the existence of stealth-adapted viruses and ii) suspension of the clinical diagnostic testing for these viruses
The concept of stealth viruses was formulated in 1990 when I had the opportunity to examine a brain biopsy from a Palm Springs’ school teacher with an unexplained severe neurological illness. In spite of a positive signal using a newly developed molecular probe assay (polymerase chain reaction or PCR), there was no inflammatory reaction (the accepted hallmark of an infectious process in an immunologically competent patient). By 1991, I had managed to culture a cell damaging (cytopathic) virus from a PCR positive patient with chronic fatigue syndrome (CFS). The virus caused cells to cluster, fuse and become foamy from lipid (fat) accumulation. A similar cytopathic virus was cultured from the cerebrospinal fluid (CSF) of a comatose patient with a 4 year history of a bi-polar manic-depressive illness. The second virus isolate was sent to the Los Angeles County Public Health Laboratory which subsequently forwarded the virus to the Californian Department of Health Laboratory.
DNA sequencing of two PCR amplified regions of the virus repeatedly isolated from the CFS patient was performed and the data published in 1994. One region showed partial, but highly significant, matching to a known sequence of human cytomegalovirus (HCMV). The other region could not be matched to HCMV. Cytopathic (cell damaging) viruses were being cultured from both blood and CSF of various other patients with neurological, psychiatric and auto-immune diseases, including autism, amyotrophic lateral sclerosis (ALS), schizophrenia and systemic lupus erythematosus. While some of these viruses showed molecular cross-reactivity with the virus isolated from the original CFS patient, other viruses were seemingly structurally unrelated. This led to the conclusion that stealth viruses comprise a broad grouping of viruses whose characteristic feature is the failure to provoke an inflammatory response in spite of being actively cytopathic in test tube cultures.
This conclusion did not sit well with traditional virologists who were accustomed to dealing with precisely definable entities with known and consistent DNA or RNA composition. Moreover, by focusing on the patient with CFS, I evoked the ire of several prominent investigators who had tried without success to culture viruses from CFS patients. Others researchers were more successful but thought that their findings simply reflected the reactivation of a conventional virus, such as human herpesvirus-6 (HHV-6), rather than revealing the primary cause of the patients’ illnesses. Nor could I satisfy those who wanted a laboratory test that would be specifically diagnostic for CFS and that could readily distinguished fatigued from non-fatigued patients; or at least would not be positive in some seemingly healthy individuals. I was far more impressed with the clearly abnormal findings, especially when observed in cultures from patients with otherwise unexplained complex illnesses. Potential infectiousness was also suggested in patients in whom family members or even household pets had developed equally complex, yet clinically diverse diseases. Any doubt about the relevance of these findings was removed when cultured infected cells were shown to cause severe non-inflammatory illness in animals. In collaboration with Dr. Tom Glass of the University of Oklahoma, we observed the virus-induced transformation of healthy cats to reclusive, pained, irritable creatures creating bald spots on their heads from constant rubbing. Again, there was no inflammation in the brains or other tissues of these animals, only the foamy, lipid-filled cells that were being seen in the viral cultures.
Extended DNA sequencing of the original virus isolate revealed a region for which there were sequence data of the cytomegaloviruses from various other species, including African green monkeys. The DNA matching to the sequence of African green monkey simian cytomegalovirus (SCMV) was extremely close, indicating an unequivocal origin of the patient’s virus from SCMV. Partial DNA sequencing of the virus from the still comatose patient with a history of a bi-polar illness showed a similar origin from SCMV.
Having worked with the Food and Drug Administration (FDA), I immediately realized that the SCMV-derived stealth viruses could have entered into the human population from monkeys used to produce live polio virus vaccines. I called the FDA with my results and learned that they were still using African green monkeys to produce polio vaccines. I spoke of my work at an FDA meeting in June 1995 attended by vaccine manufacturers. I also wrote to the President of Wyeth about my research. I petitioned both FDA and CDC with unsolicited proposals to test polio vaccine lots and to request funding to continue DNA sequencing. Both proposals were dismissed. I presented my findings again to an Institute of Medicine meeting in November 1995. A lawyer immediately filed a legal suit against Wyeth for me to receive the polio vaccine lots administered to some of his clients with neurological diseases. He knew of an ongoing challenge by the mother of a stricken child who had surprisingly won a court order (resisted by both Wyeth and FDA) to have the vaccine she had received tested for human immunodeficiency virus (HIV). The court order specifically excluded any additional testing, including testing for monkey viruses. The lawyer involved in this case had recently arranged for me to receive a blood sample from the child for stealth virus testing. The lawyer could use a positive test result to seek an expansion of the scope of the court mandated testing on the polio vaccine lot administered to the child.
These events were too much for the Establishment. On November 15th, I was told by my University Department Chairman that he had closed my laboratory, dismissed all of the volunteers, and taken the more than $22,000 from my research account. The money he said had gone for back pay and pay-in-lieu of notice for the licensed medical technologist. The funds had been in a USC Gift Account specifically earmarked to trace the possible SCMV origin of cultured stealth viruses. I strongly protested the misappropriation of the patient donated funds and refused to sign a waiver of the University’s action. I knew the Department Chairman had received major funding from a subsidiary of Wyeth and felt suspicious that his abrupt actions were essentially in response to industry pressure. The blood sample from the sick child arrived on November 17th. I managed to store it and showed it was culture positive by temporarily spending time in the Los Angeles County Public Health Laboratory. I subsequently learned that the child had a brain biopsy. Although a diagnostic quandary to his treating physicians, it showed the vacuolated, foamy cells that I had come to recognize from earlier patients and from the virus inoculated cats. The child further deteriorated following the surgery and died.
I took leave from USC in January 1996 when confronted with demands for an additional $15,000 before my laboratory would be reopened. This amount was said to reflect the University’s overhead on the money disbursed from the Gift Account. It was also made clear that I could not resume any patient related testing. Under considerable duress, I eventually located a laboratory in a closed, bankrupt hospital and moved what equipment I could claim as my own into this facility. USC held firm to their insistence that any equipment I had purchased from prior grants belonged to the University.
Assisted by Zaki Saluhuddin, the discoverer of the HHV-6 virus, and by other volunteers, underpaid technicians, and a medical technologist, I was able to pursue the task of understanding the nature of stealth-adaptation and focus on how the diseases might best be treated. The laboratory was designated the Center for Complex Infectious Diseases or CCID. It was licensed under the Clinical Laboratory Improvement Act (CLIA) without any deficiencies cited in inspections held in 1996, 1998 and 2000.
Zaki Saluhuddin left in 1998 but not before he had independently validated the stealth virus testing in double blinded studies. Similar double-blinded validations were independently performed by Dr. Robert Gan, Ph.D., Russell Collins, CLS, and on various occasions by myself (with the help of an assistant to code the samples). As we all knew, positive tests were neither disease specific nor confined to patients with severe illnesses. Still a positive test was clearly and unmistakably abnormal. As an example, I recall in 1996 showing a positive culture to the technologist in the Virology Section of the Los Angeles County Public Health Laboratory. She immediately recalled seeing a similar cytopathic effect from a much earlier culture. As she retrieved her records it turned out to be the sample sent to her in 1991 from the comatose patient with the history of a bi-polar manic depressive illness.
DNA sequencing data continued to substantiate the model of stealth-adaptation as the loss or mutation of the relatively few genes that code for components that are recognized by the cellular immune system. Most virologists have yet to appreciate that since individual lymphocytes recognize distinct antigens, effective immune recognition of virally infected cells requires multiple copies of a few viral antigens at the cell surface rather than a plethora of many antigens that would impede effective lymphocyte binding. For example, approximately 60% of the anti-human cytomegalovirus cytotoxic T lymphocytes recognize the protein coded by the Unique Long segment gene number 83 (referred to as UL83). Twenty-five percent recognize UL55 and another 10% the UL123 protein. Deletion or mutation of these three genes and one can arrive at a virus that will not be effectively recognized by the cellular immune system. Stealth-adapted viruses show additional properties including the apparent capacity to assimilate other genes that can include genes of bacterial origins and cellular genes that can potentially cause cancer.
It is difficult to exaggerate the potential Public Health significance of the stealth-adaptation process to the microbial threat posed to mankind. The production of live vaccines, especially in tissues from foreign species, such as the use of African green monkeys to produce live polio vaccines, could clearly facilitate stealth-adaptation. Armed with an insider’s knowledge of the vaccine industry and the influence it can have on public policy, I continue to believe the message will eventually get through. On each trip to Washington or Atlanta, I make a point of visiting FDA or CDC, respectively. The following unanswered e-mail sent August 2000 to the then CDC Head of Herpesvirus Research (Dr. Phil Pellett) following a herpesvirus conference is typical:
“Dear Phil, Thank you for the discussion during the last evening of the International Herpesvirus Workshop. You were willing to talk "bluntly," yet in a constructive manner, regarding CDC shunning of my research. As you said, CDC administrators look to you for scientific judgment on matters relating to herpesviruses. Without your support, there is little chance of any response to my requests that CDC pursue what I perceive to be a major Public Health problem. As I recall, the major points of our discussion were as follows: You spent approximately 45 minutes at my poster and came away with the impression that some of the sequence data must be incorrect. You were concerned that sequence homology matching should be more uniform and not differ along a stretch of nucleotides. You asked if all of the sequencing had been fully double-stranded and whether I had reviewed all of the primary data. I indicated that most of the extended sequencing had been performed by Lark Technologies, at Houston Texas. While there was some internal overlapping, the sequences were primarily derived from one-way reactions. While, there is the possibility of an occasional nucleotide error, this would have had no effect on the conclusions that I was drawing from the data. I understand that you hold your own sequence-related studies up to a particularly rigorous standard, but this has more to do with the types of conclusions that you are trying to draw, rather than justifying dismissing any sequences that are not verified by double-stranded confirmation. Most of the sequences have been on GenBank for a long time and can be reviewed directly by anyone who's interested. The irregular matching that you noted is indeed interesting and goes along with an earlier publication on the genetic instability of the virus. You also suggested that real science ought to be obvious to the intelligent scientist and that it was my responsibility to present the work so that it would be more widely accepted. Again I disagree. Most scientists are pretty fixed in their belief system, and historically any shift in a prevailing paradigm is met with resistance. The average scientists can not be expected to plow through loads of someone else's raw data, or as you said "interpret my data for me." The CDC is something of an exception, however, since its mission is to be vigilant for possible threats of emerging infections. The poster provided a good opportunity for a scientific discussion, but you chose to view it in my absence. I, therefore, do not know if you fully understood and appreciated the significance of what was being presented. I was surprised by your suggestion that I sought a chance to discuss my work at CDC as a "cheap" way of claiming CDC recognition. I view my challenge as primarily to get CDC to listen and to take some action. I hope you will continue to provide some assistance by engaging in more meaningful discussions of actual sequence data and patients' histories. In particular, I would like to know your responses to the following issues that I have raised. 1. Do you doubt that the virus for which I have extensive sequence data, was derived from an African green monkey simian cytomegalovirus. 2. Do you doubt that the virus came from a patient, or that it can induce severe illness when inoculated into cats. 3. Are you convinced that the virus has some unusual sequences that at least qualifies it as being an atypically structured virus. 4. Do you feel the apparent absence of UL83 and UL55 related genes could provide the virus a way of evading recognition by the cellular immune system. 5. Are you willing to accept that the virus has recombined with cellular sequences, including the CXC chemokine coding gene, melanoma growth stimulatory activity, a potential oncogene. 6. Do you see any significance in the apparent amplification of the US28 chemokine receptor coding gene. 7. Do you accept the presence of bacteria-derived sequences within the viral genome. 8. Are you aware of the high proportion of patients with unexplained encephalitis-like illnesses, including cases in which brain biopsies have been submitted to CDC for review. 9. Given our positive tissue culture findings in such patients, can you dismiss the possibility that these patients are infected with atypically structured viruses. 10. Don't you think we owe it to those responsible for the Nation's Public Health to have some of these topics more openly discussed_ Enough questions for now. Most of the papers dealing with stealth-adapted viruses are on the web site www.ccid.org I hope we will continue to dialogue and thanks again for the time provided in Portland. Kind regards, W. John Martin, M.D., Ph.D.”
The stakes with CDC got higher when I identified a potential linkage between the testing of cytomegalovirus contaminated polio vaccines in Africa and the emergence of HIV from simian immunodeficiency virus (SIV). This connection was based on the increased number of US28 genes in both SCMV and rhesus CMV that provide a receptor for the cellular entry of HIV and SIV. CDC had been storing sera from early polio vaccine studies in the Congo. Analysis of these stored sera could show that the vaccine used in Africa was indeed contaminated. Complacent bureaucrats are reluctant to bring skeletons out from the closets, such as the 1972 study showing that all 11 African green monkeys tested jointly by Wyeth and FDA were infected with SCMV, or the CDC employee who told me of CDC culturing SCMV from a recipient of an experimental rubella vaccine.
Doing scientific battle to learn some of Nature’s secrets is fun and uplifting. Interacting with Government officials can be frustrating, but at least the Government is in the position of achieving major Public Health changes. Assisting patients and especially children with baffling illnesses is a rewarding privilege especially when the promise of research justifies continuing optimism. On the other hand listening to patient support group advocates wanting to promote their own financial needs, and having to deal with a few dishonest, vindictive patients seeking some perceived entitlement for their sorry state, are decidedly negative experiences. I refused to perform a stealth virus culture on a patient who had been previously tested at USC. The patient was intent on using a positive result to justify receiving ganciclovir, a potentially toxic anti-viral drug, and yet was not being seen by an infectious disease specialist. There were also the confounding issues of possible Lyme disease, babesia infection, multiple previous diagnoses and anger at the medical system’s failure to provide effective therapies.
Seemingly based on prior CDC communications and triggered by this disgruntled patient, the California Department of Health conducted a CLIA inspection of the laboratory in 2002. My detailed responses to a series of stated deficiencies were deemed inadequate and the matter was referred to the Center for Medicare and Medicaid Services (CMS), the Federal body that issues CLIA certificates. They suspended the CLIA License. I did not appeal the finding mainly because a failed appeal leads to a two year disqualification rather than a suspension. In addition, I could not get a straight answer whether a cytopathic effect seen in culture would ever be accepted as adequate evidence for the presence of a reportable abnormality. As indicated in the following series of letters sent to CMS, I wholeheartedly tried to use the inspection process to raise the Federal Government’s Public Health concern that our Nation is in the midst of a serious epidemic. Copies of all letters (sent on CCID letterhead) to CMS regarding CLIA inspection July 24, 2002 Dear Karen, In good faith, I provided the California Department of Health and your Office a comprehensive response to a Statement of Deficiencies. My response was received by the State on Monday afternoon. Yesterday, I was notified by Fax that my response was unsatisfactory and a recommendation for sanctions has been forwarded to your Office. I trust your Office will not be so quick to judgment. I would like to work within the system to "establish the existence of atypically structured cytopathic viruses and to demonstrate a culture method for their detection." In this regard, I have reviewed the Inspector General Report on CLIA Regulation of Unestablished Laboratory Test. I realize that CMS does not validate tests and I am not asking you to do so. What I would like, however, is to have your support and guidance in my interactions with Los Angeles County Public Health Laboratory, CDC and CMS. The Nation's health is our common goal. Before you take any action, I would appreciate an opportunity for an introductory phone conversation. I would also like to contact the author of the Inspector General's report. Some years ago it was suggested that I apply for a "Demonstration Project" with HCFA. I will also see if I can present the work at CDC and NIH. It would be encouraging if some of these efforts were to become part of your determinative process. I look forward to contacting you later today.
I had a pleasant and constructive telephone conversation with Ms. Karen Nickel, Head of the Laboratory Field Services of the California Department of Health. She kindly explained that repeated complaints had been received by the Health Department concerning CCID and in particular the testing for stealth viruses. The complaints came from CDC, certain State Health Departments and individual physicians. The complaints were essentially that patients were being misled into believing they were infected with viruses that did not exist. The California Department of Health was in no position to question the opinion of CDC or to assess how the testing was being used, or possibly abused. Staff shortage prevented action being taken last year, but with continuing complaints, closure of the laboratory was given a higher priority this year. Consequently, the California Department of Health undertook a Laboratory Field Service inspection with a predetermined outcome. I was not surprised by this forthright explanation. Clearly I need to address the concerns of CDC. For several years, I have been trying to engage CDC in a scientific evaluation of my work. I believe the data are irrefutable, but they obviously can be ignored. In March of this year, I presented a Poster at a CDC sponsored International Workshop on Emerging Infectious Diseases. Disappointedly, it did not evoke further inquiry. I had prepared more data for an International Herpesvirus Workshop that I was unable to attend because of the limited time allowed to respond to the inspection report. At this stage, I am seeking the opportunity for an informal seminar at CDC at which I could present the data and answer questions. I would also like to demonstrate the culture techniques to laboratory technologists. CMS is in a justified position of helping me by asking for CDC input as to whether my data "establish the existence of atypically structured cytopathic viruses." I really want to get CDC, FDA, NIH and others involved so that I can pursue hopeful leads regarding potential therapies. I am including a copy of the poster that I had presented last March. Sincerely, W. John Martin, M.D., Ph.D. cc. Karen Nickel August 7, 2002
The extent of cellular abnormalities seen in positive cultures is far beyond any of the changes ever seen in an uninoculated culture. I have taken a series of illustrative photographs as part of an ongoing validation study. I will send you and the State copies by regular mail for review. As stated in my previous correspondence, uninoculated cultures were included in each experiment with written documentation of a lack of cytopathic activity included in the sterility quality control that was performed on each batch of MRC-5 cells received. Sincerely,
August 11, 2002 Ms. Karen Fuller, Sincerely,
Ms. Karen Fuller, There was no difficulty
in distinguishing a positive from a negative culture I have typically saved an aliquot from many of the samples that I have tested over the last several years. I can repeat the study at any time intervals that you feel is appropriate. I can also send both positive and negative aliquots of previously tested processed blood samples to an outside laboratory. Among the selected photographs of positive cultures, several show the types of lipid crystals commonly seen in positive cultures. Other photos show the ribbon-like structures and the pigmented aggregated inclusions. I hope this information will forestall the imposition of sanctions, so that I can learn to better understand the clinical importance of such striking findings. Sincerely, W. John Martin, M.D.,
Ph.D. I have shown the CPE to several bench technologists. It is not that they have not seen the changes, it just that they did not know how to interpret the changes. The waning of the CPE in infrequently fed cultures has also encouraged a disregard for the changes. Some other patients have been told they have an atypical CMV infection. Additional support for an involvement of atypical herpesviruses in CFS patients is provided by clinical trials that use anti-herpesvirus drugs. For example a patent was recently issued to Dr. Martin Lerner on valganciclovir therapy in CFS patient. A brief summary of the patent is as follows:
United States Patent
6,399,622; Lerner June 4, 2002. I also spoke today with Dr. John Stewart of CDC. He is circulating my poster among their virologists. Given the current concern about West Nile virus, I suspect there will be strong interest in my work. It is known for example that herpesviruses can be activated by West Nile virus and that dual infection is more serious than either infection alone. I trust this information is helpful in your deliberations and that you will not abruptly close CCID clinical laboratory. I will work diligently with you and the State if their are remaining Condition-Level deficiencies or concerns. Sincerely,
October 12, 2002 Dear Karen, I am responding to your letter dated October 9, 2002. I did not pursue the option of appealing your determination primarily because of the punitive consequence of an unsuccessful appeal. Culture results from CCID have only been recorded and reported from cultures that were completed prior to August 27, 2002. In anticipation of reestablishing a diagnostic service, that I truly believe will be of potential Public Health value, I would appreciate clarification on the following issue: The phase "all patient testing operations" appears to me to be broader than the stipulation of allowing to "test human specimens but do not report patient-specific results for the diagnosis, prevention, or treatment of any disease or impairment of, or the assessment of the health of, individual patients." Especially given a challenge of needing to submit "a credible allegation of compliance and … acceptable evidence of correction" the opportunity should exist for some additional testing. Specifically, could you please clarify for me which if any of the following are acceptable practices given the current suspension of the CLIA certificate. 1. Testing my own blood
sample. 9. Testing samples collected from animals. The way the Attestation is written is somewhat confusing and possibly open to misunderstanding. I have noted the enormity of the penalty and have no interest in violating CLIA laws. May I ask, however, for you to incorporate your responses to the above questions into a more clearly defined use of the term "patient testing" in line 4 of the Attestation. I am not a lawyer and will still probably need to have some help in interpretation of the revised document. I will be in Washington D.C. for the week of October 20th and will be spending most of this week preparing for this trip. If possible, I would like to delay final signing of the attestation till the following week. No experiments will be performed in the interim period. The web site is managed by a volunteer. I have conveyed to her the need to make additional changes to the web site in accordance with your instruction. For various reasons, this too may take her several days. Sincerely, W. John Martin, M.D., Ph.D. 3-3-2003
Dear Karen, I read your response on March 1, 2003, having been away from the laboratory during the week. I fully understand that "a laboratory that reports any patient-specific results, either in writing or verbally, must have a valid CLIA certificate in effect." I note CLIA’s unwillingness to accept statements that "no verbal or written report would be issued," or that test results "would not be communicated to the patient or their physician." There is apparently an underlying presumption that having access to a patient identity is essentially equivalent to relaying results of any research testing to the patient or to the patient’s physician. You have my assurance that I wish to remain in full compliance with all CLIA mandated laws. I have not reported any results to patients or physicians for any testing performed since suspension of the CLIA license. Nor have I maintained any patient identification records for the few samples that were occasionally delivered to the laboratory since the CLIA suspension. Sincerely, W. John Martin, M.D., Ph.D.
I, Russell Collins am a duly licensed clinical laboratory scientist. I have known Dr. W. John Martin for over 5 years and have been a staff member of the Center for Complex Infectious Diseases (CCID) since September 1999. I can attest to the following facts: CCID has conscientiously and reliably performed clinical laboratory testing on human and on occasional animal derived blood samples for evidence consistent with the presence of a viral infection, of the type referred to as a stealth-adapted virus. The primary indication for the presence of such viruses is the ability of the sample to induce characteristic cellular damage in cultured fibroblast cells. The type of damage being sought was the development of foamy vacuolated cells that form clusters, and that commonly become pigmented. This type of change occurs with known stealth-adapted viruses, including the well characterized virus that Dr. Martin had previously isolated from the patient with initials D.W. I have personally
performed numerous stealth virus cultures that were requested by Dr. Martin and
other physicians. Most of the testing was done on blood samples obtained from
patients, but on occasions were done on control individuals, including blood
donors. I have also tested several blood samples from patient D.W. End of Letters to CMS Upon reflection, I was spending so much time doing the cultures that I was not doing justice to the observations that had already been made. I set about writing two overdue manuscripts on alternative cellular energy pigments (ACE-pigments). I also set about learning enough physics to call myself a biophysicist. I began to meet a wonderful array of individuals, including the gentleman who kindly provided the MI-Hope non-profit foundation. It became the BioPhysics Institute and then S3Support. Other individuals have each contributed to an understanding of stealth viruses that I would probably not have gained from continuing with diagnostic cultures. More importantly, I now see a clear rationale for well designed “energy medicine” based clinical trials. Possibly only when a therapy is proven will our Public Health system be willing to address the likelihood of a widespread infectious component impacting on our Nation’s health. For now, I feel patients should at least expect the Government to be performing stealth virus cultures. The methods are fully described in various publications and the original stealth virus has been available from the American Type Culture Collection (ATCC) since 1992. There is a serious epidemic and it needs to be officially addressed. |